8-23246786-A-T

Variant names:

• chr8-23246786-A-T
• rs754334360
• NM_152272.5:c.91A>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_152272.5(CHMP7):​c.91A>T​(p.Met31Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000007 in 1,429,546 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: CHMP7 NM_152272.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.15
• Publications: 0 publications found

Genes affected

CHMP7 (HGNC:28439): (charged multivesicular body protein 7) Involved in several processes, including late endosome to vacuole transport; midbody abscission; and mitotic nuclear division. Located in cytosol; nuclear envelope; and nucleoplasm. Part of ESCRT III complex. Colocalizes with chromatin. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHMP7	NM_152272.5	c.91A>T	p.Met31Leu	missense_variant	Exon 2 of 11	ENST00000397677.6	NP_689485.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHMP7	ENST00000397677.6	c.91A>T	p.Met31Leu	missense_variant	Exon 2 of 11	1	NM_152272.5	ENSP00000380794.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 198668 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.00e-7 AC: 1 AN: 1429546 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 708342

African (AFR) AF: 0.0000306 AC: 1 AN: 32642

American (AMR) AF: 0.00 AC: 0 AN: 39750

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25542

East Asian (EAS) AF: 0.00 AC: 0 AN: 37598

South Asian (SAS) AF: 0.00 AC: 0 AN: 81848

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50882

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5600

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1096536

Other (OTH) AF: 0.00 AC: 0 AN: 59148

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Uncertain	0.091	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	27
DANN	Benign	0.94
DEOGEN2	Benign	0.10	T;T;T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.65	.;T;T
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.57	D;D;D
MetaSVM	Benign	-0.75	T
MutationAssessor	Uncertain	2.1	M;M;.
PhyloP100		6.2
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.9	N;N;N
REVEL	Benign	0.25
Sift	Benign	0.037	D;D;T
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.98	D;D;.
Vest4		0.49
MutPred		0.60		Loss of catalytic residue at M31 (P = 0.0022);Loss of catalytic residue at M31 (P = 0.0022);Loss of catalytic residue at M31 (P = 0.0022);
MVP		0.57
MPC		0.63
ClinPred		0.94	D
GERP RS		5.8
PromoterAI		-0.044	Neutral
Varity_R		0.72
gMVP		0.85
Mutation Taster		=59/41	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs754334360; hg19: chr8-23104299;